Micronized Purified Flavonoid Fraction Research Articles

Hemorrhoidal disease among doctors from grade-A tertiary hospitals in big cities of China: results from web-based doctors as patients survey

BackgroundDoctors are at high risk of developing hemorrhoidal disease (HD), but it is unclear whether doctors are aware of this risk. The OASIS (dOctors AS patIentS) study was performed to examine the prevalence, awareness, diagnosis, and treatment of HD among doctors in big cities in China.MethodsAn online survey consisting of a structured questionnaire was carried out among doctors in grade-A tertiary hospitals in 29 provinces across China from August to October 2020.ResultsA total of 1227 questionnaire responses were collected. HD prevalence was 56.8%, with a significant difference between internists and surgeons (P = 0.01). 15.6% of doctors with HD didn’t have serious concerns about the recurrence and severity of HD. 91.5% of doctors adopted general treatments, and 83.0% considered oral medications only when topical medications were ineffective. Among the oral medications, Micronized Purified Flavonoid Fraction (MPFF) was most effective based on the scores from three important parameters, but only 17% of doctors received MPFF.ConclusionsDoctors are at higher risk of developing HD with a high prevalence among Chinese doctors, but they are not fully aware or not concerned about HD. There is a deficiency in treatment recommendations and clinical management of HD even for doctors, including late initiation and inadequate oral drug therapy. Therefore, awareness and standardized treatment of HD should be improved among Chinese doctors, as well as in the general population.

Phlebopathies: from pathogenesis to treatment

Introduction. The prevalence of phlebopathies varies from 15 to 31%. The QoL of patients with phlebopathies is impaired. Phlebotropic therapy is the main method for treating phlebopathies. Aim. Evaluation of the efficacy and safety of micronized purified flavonoid fraction (MPFF) (Troxaktiv). Materials and methods. A total of 129 females aged 18 to 45 years (average age of 35,2 ± 4,1 years) were included in the open observational study. To exclude pathology of the principal veins of the lower extremities, all patients underwent ultrasound examination, as well as photoplethysmography with automatic measurements of the venous refilling time and the power of the calf muscle-venous pump. All patients were divided into three groups: Group 1 received MPFF at a daily dose of 1000 mg only, Group 2 – class I compression hosiery in addition to MPFF, Group 3 – a course of psychotherapy and guidelines on lifestyle changes, augmentation of physical activity, etc.Results. Due to ongoing treatment measures, positive changes with decreased number of complaints and their intensity were observed. Positive changes occurred mainly in the groups of patients receiving phlebotropic therapy and combined phlebotropic/compression therapy: the number of patients with vein-specific symptoms decreased by more than half, while 31 patients reported the persistence in complaints at baseline level or their slight decrease while taking psychotherapy course and lifestyle changes. The specific therapy groups reported a significant dynamic reduction in the feeling of heaviness and pain as well as night cramps in the calves. Discussion. In the presented study, the patients were prescribed MPFF/Troxaktiv™ at a daily dose of 1000 mg, both as monotherapy and in combination with compression. A significant decrease in the frequency and severity of vein-specific symptoms and a significant increase in the patients’ quality of life was recorded in both of these groups. Photoplethysmography results showed an improvement in elastic rebound properties of the venous wall. All patients were satisfied with the treatment. Conclusion. MPFF/Troxaktiv™ has demonstrated high efficacy and safety in the treatment of patients with phlebopathies of various origins.

Cardiovascular Insights for the Appropriate Management of Chronic Venous Disease: A Narrative Review of Implications for the Use of Venoactive Drugs.

Evidence suggests that chronic venous disease (CVD) may be a cardiovascular disorder, as patients with CVD are prone to developing arterial (atherosclerosis) and venous (thromboembolism) diseases. This may be partly explained by shared risk factors. Thus, patients with CVD or cardiovascular disease require careful history-taking and physical assessment to identify coexisting pathologies and risk factors. This article summarises a symposium at the XIX World Congress of the International Union of Phlebology held in Istanbul, Turkey, in September 2022. Common pathophysiological features of CVD and cardiovascular disease are endothelial injury, hypercoagulability and systemic inflammation. In CVD, inflammation primarily affects the microcirculation, with changes in capillary permeability, vein wall and valve remodelling and increase in oxidative stress. Once patients develop symptoms/signs of CVD, they tend to reduce their physical activity, which may contribute to increased risk of cardiovascular disease. Data show that the presence of CVD is associated with an increased risk of cardiovascular disease, including peripheral arterial disease and heart failure (HF), and the risk of adverse cardiovascular events increases with CVD severity. In addition, patients with cardiovascular disease, particularly those with HF, are at increased risk of venous thromboembolism (VTE) and should be assessed for VTE risk if they are hospitalised with cardiovascular disease. Therefore, CVD management must include a multi-specialty approach to assess risk factors associated with both the venous and arterial systems. Ideally, treatment should focus on the resolution of endothelial inflammation to control both CVD and cardiovascular disease. International guidelines recommend various conservative treatments, including venoactive drugs (VADs), to improve the symptoms/signs of CVD. Micronized purified flavonoid fraction (MPFF) is a VAD, with high-quality evidence supporting its use in relieving symptoms/signs of CVD and improving quality of life. Moreover, in large-scale observational studies, MPFF has shown superior effectiveness in real-world populations compared with other VADs. Video Abstract. (MP4 97173 kb).

Results of preoperative application of micronised purified flavonoid fraction as part of a multimodal analgesic regimen in anorectal surgery: a prospective, randomised, placebo-controlled, double-blind study

This study aims to assess the efficiency of micronised purified flavonoid fraction (MPFF) administration prior to open haemorrhoidectomy on postoperative pain severity reduction.Methods. The prospective clinical study involved patients with haemorrhoidal disease. Participants were randomly divided into two groups: the first one received 1000 mg of MPFF (Detralex®) 15 days before surgery, seven days after surgery, according to the acute haemorrhoid treatment scheme, and 1000 mg per day until 30 days after surgery; the second one received a placebo. The primary endpoint was the frequency of opioid intake.Results. The study included 182 participants (102 and 82 in the experimental and control group, respectively). Postoperative pain at rest and during defecation was significantly lower in the experimental group on days 6—9 postoperatively (p < 0.05). The use of opioids and other NSAIDs after surgery did not differ between groups. There was no significant difference between groups in side effects frequency and time to return to the usual lifestyle. As for the quality of life, the control group had significantly higher levels of self-care difficulty, anxiety and lingering pain/discomfort, being more likely to suffer from other persistent complaints.Conclusion. The preoperative administration of MPFF as analgesia has demonstrated safety and efficacy, effectively reducing postoperative pain in anorectal surgery while avoiding an increase in side effects. Hence, it is recommended for routine implementation in patient care as an essential component of multimodal analgesia during anorectal surgery.

Improving Chronic Venous Disease Management with Micronised Purified Flavonoid Fraction: New Evidence from Clinical Trials to Real Life.

Chronic venous disease (CVD) develops in the microvessels, and is perpetuated by a vicious cycle of inflammation and endothelial activation, structural and functional changes to vessels and valves, and progressive venous hypertension. Data from animal models indicate that micronised purified flavonoid fraction (MPFF) has beneficial effects on a range of pathophysiological processes that contribute to CVD, including inflammation, micro-vessel permeability, valve and vessel wall remodelling, and reflux in microvalves. These effects explain its beneficial effects on the signs and symptoms of CVD, which have been seen across the spectrum of Clinical, Etiological, Anatomical and Pathophysiological (CEAP) categories of CVD severity. This includes patients with symptoms but no detectable anatomical or pathophysiological anomalies (C0s or C1) and patients with varicose veins (C2). In addition to symptomatic improvement, MPFF has been shown to reduce oedema in patients with C3 CVD, resolve skin symptoms in patients with C4 CVD, and accelerate the healing of venous ulcers in patients with C6 CVD. MPFF is highly recommended in international guidelines of CVD management and is the only veno-active drug to receive guideline endorsement for an improvement in patient quality of life.

Intramammary Infusion of Micronised Purified Flavonoid Fraction (MPFF) in Mastitis-Diagnosed Dairy Cows Naturally Infected by Staphylococcus spp. in the Late Lactation.

Infectious mastitis is the most prevalent health problem in dairy cattle that can result in permanent economic losses on dairy farms. The micronised purified flavonoid fraction (MPFF) is a biocompatible active polyphenolic compound derived from flavonoid glycosides which exhibits several antimicrobial, anti-inflammatory, and phlebotonic properties. The goal was to assess the effects of an alternative therapy for mastitis based on MPFF intramammary infusions in late lactation in dairy cows naturally infected by Staphylococcus spp. The California Mastitis Test (CMT scores) was performed to detect mastitis-positive quarters in twelve dairy farms. All cows were screened for immune response by measuring somatic cell counts (SCCs; cells/mL) in milk samples from each quarter. In addition, bacteriological identification, pathogenic bacterial isolates, and total bacterial counts (TBCs; CFU/mL) were assessed before (day 0, last milking day) and after (day 3 post-calving) MPFF application. Antimicrobial sensitivity patterns of the pathogenic isolated bacteria were evaluated. Finally, cure rates (%) were determined for each MPFF treatment. Around 15 mastitis-related genera were isolated. Staphylococcus aureus (25.2%) and coagulase-negative Staphylococci (CNS; 22.4%) were the most prevalent pathogens. No statistical differences were observed in SCCs and TBCs after low, medium, and high MPFF dose administration in S. aureus-positive mastitis cases (p > 0.05). However, differences were observed in SCCs and TBCs after medium and high MPFF dose administration in CNS-positive quarters (p < 0.05). The pathogenic bacteria isolate reduction after MPFF applications showed a dose-response fashion (p < 0.01) while isolates obtained from controls and low MPFF-treated quarters remained similar, irrespective of the pathogen (p > 0.05). Sensitivity patterns were variable, although S. aureus remained resistant, irrespective of the MPFF dose. However, CNS showed a dose-response sensitivity pattern. Finally, the cure rate (%) on day 3 post-partum improved significantly using medium and higher MPFF doses in CNS-positive quarters (p < 0.05). In conclusion, MPFF treatment was found to be more effective for CNS-positive cases in the late lactation due to noticeable dose-specific responses regarding somatic cells, bacterial counts, sensitivity patterns, and cure rates in dairy cattle.

Challenge in prominent grade IV hemorrhoid management: a case report

Background: Management of grades 1 and 2 of internal hemorrhoids is non-operative by advising the patients to have a high-fiber diet and take phlebotropic agents such as MPFF (Micronised Purified Flavonoid Fraction). Rubber band ligation is the alternative in case of failure office-like procedure sclerotherapy. Management of grade 3 and 4 internal hemorrhoids is operative management. The gold standard of hemorrhoid surgery is the Morgan Milligan method, an excisional surgery, since this method results in a low recurrence rate. Case presentation: We presented a twenty-six-year-old male patient who came to St Elizabeth Hospital, Semarang, with a chief complaint painful lump in the anal canal for the past 7 days. For about 3 years, he got chronic spontaneously reducible anal pile and bleed, and since 2 months, the pile has enlarged and only can be reduced manually. Since 7 days ago, nonreducible anal lump (prolapse). He was several times treated medically by General Practitioner. The patient was in good condition on physical examination but looked painful with VAS: 7. The anal region looked like a big prolapsing anal canal skin and mucosa with a dentate line in between. The lump looked hyperemic, with edema and some thrombus. Conclusion: Management of big grade IV internal hemorrhoids is challenging. Combination Morgan Milligan for a big pile and HAL-RAR for the rest of the pile gives a good result. The administration of MPPF one gram three times daily, pre and post-operatively, reduce the edema, post-operative pain and risk of bleeding, which is clinically significant.

COVID-19-associated phlebopathy as a current problem of modern phlebology

Введение. SARS-CoV-2 сопровождается развитием дисфункции венозного эндотелия, которая может привести к развитию персистирующей флебопатии нижних конечностей, снижаю щей качество жизни пациентов.Цель. Оценить эффективность фармакологической терапии пациентов с постковидной флебопатией.Introduction. SARS-CoV-2 is accompanied by the development of venous endothelial dysfunction, which can lead to the development of persistent phlebopathy of the lower limbs, reducing the quality of life of patients.Objective. To evaluate the efficacy of pharmacological therapy in patients with postcocclusive phlebopathy.Materials and methods. 178 patients (125 women), mean age 34.8 ± 3.2 years, who underwent SARS-CoV-2, for their first veno-specific complaints received micronized purified flavonoid fraction (MPFF) 1,000 mg per day for 90 days. Complaints were monitored using a 10-cm visual analog scale and the CIVIQ-20 questionnaire. All patients underwent ultrasound examination of the venous system of both lower extremities and photoplethysmography. Laboratory biochemical examination with determination of endothelial dysfunction marker levels was performed in 30 patients before and after treatment.Results. After 90 days of phlebotropic therapy, there was a significant reduction in the severity of all venous-specific complaints, except for intradermal vein dilation. The global quality of life index increased from 64.4 ± 11.2 to 86.6 ± 9.1% (p &lt; 0.001). There was an improvement in photoplethysmography (PPG) scores. Return blood-flow time and tibial venous muscle pump strength increased significantly (p &lt; 0.05) by 4.3 s and 3.5%, respectively. The 30 patients who underwent biochemical examination in the first blood samples obtained from the great saphenous vein showed a significant increase in IL-1 concentration (7.8 ± 0, 7 pg/ml), IL-6 (18.7 ± 1.8 pg/ml), VEGF (187.8 ± 11.6 pg/ml), TNF (7.8 ± 0.9 pg/ml), histamine (22.4 ± 11.4 nmol/L) and hsCRB (5.4 ± 0.3 mg/L), indicating that a proinflammatory phenotype of venous endothelium was formed. After 90 days of MOFF administration, these indices significantly decreased. The levels of IL-1 and IL-6 decreased by 3.2 and 10.4 pg/ml, respectively, the values of VEGF and TNF decreased by 114.6 pg/ml and 2.9 pg/ml. There was a gradual normalization of histamine and hsCRB to 6.1 ± 4.1 nmol/L and 1.1 ± 0.9 mg/L.Conclusions. The data obtained indicate that the appearance of veno-specific symptoms and syndromes in patients who have undergone SARS-CoV-2 may be due to the development of phlebopathy, the correction of which requires the use of pharmacological drugs with relevant mechanisms of action.

New Perspectives on Micronised Purified Flavonoid Fraction in Chronic Venous Disease: From Microvalves to Clinical Effectiveness.

The importance of chronic venous disease (CVD), as a cause of reduced quality of life and increased costs to healthcare systems, is expected to rise in parallel with population aging and the increasing prevalence of obesity. Venoactive drugs (VADs) are frequently used to treat the symptoms and signs of CVD. The most commonly used and widely studied VAD, micronised purified flavonoid fraction (MPFF), is effective at all stages of CVD, and has been shown to significantly reduce leg pain, leg heaviness and swelling, as well as ankle oedema and functional discomfort, in clinical trials. Recently, experiments employing animal models of CVD have demonstrated that MPFF has anti-inflammatory and venotonic effects at the microvalve level, and a pilot clinical study in patients with CVD has provided support for these findings. Collectively, these results suggest that early initiation of MPFF treatment may have the potential to favourably alter the clinical course of the disease, although further clinical data are required to confirm these findings. International guidelines on CVD management strongly recommend MPFF to reduce symptoms and improve quality of life. Studies are now needed to investigate the impact of long-term treatment on disease progression.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-022-02218-x.

Effects of Intrauterine Infusion of Micronised Purified Flavonoid Fraction (MPFF) in Metritis-Diagnosed Dairy Cows Naturally Infected by E. coli during the Early Postpartum.

Simple SummaryThe occurrence of early metritis (EM) in dairy cattle causes serious economic losses. The treatment effectiveness for EM is highly controversial. Antibiotics administered by intrauterine infusions have been extensively used to control the growth of aerobic and anaerobic bacteria. Flavonoid glycosides (FGs) are polyphenolic naturally derived compounds considered to have many health-related properties such as antibiotic, anti-inflammatory, phlebotonic, and several vascular-protecting activities. Although FGs have been used for several therapies in humans, there is an increasing interest in investigating PGs for other therapeutic purposes. The objective of the present study was to investigate an alternative treatment for EM based on FG intrauterine infusions during the early postpartum period in dairy cows. FG administration contributed to the onset of uterine and cervix involution, bacteriological and immunological control, and fertility improvement associated with highly dose-specific responses during the early postpartum period in EM-positive dairy cattle.The occurrence of metritis during the postpartum period causes serious economic losses in dairy cattle. The Micronised Purified Flavonoid Fraction (MPFF) is a polyphenolic flavonoid compound which is considered to have many health-related properties such as antibiotic, anti-inflammatory, phlebotonic, and several vascular-protecting activities. The aim was to evaluate the effects of a new strategic therapy for metritis based on MPFF intrauterine infusions during the early postpartum in dairy cows naturally infected by Escherichia coli. The clinical effects on reproductive anatomical structures and chronological involution dynamics were monitored until day 24 postpartum by ultrasonography. Moreover, uterine bacteriological and cytological (polymorphonuclear neutrophils; PMNs) profiles were analysed before and after MPFF infusion. The results showed that the success rate (% cure) at day 24 postpartum was improved significantly when using higher MPFF doses (p < 0.05). Moreover, MPFF treatment acutely diminished the size of the cervix and uterus and improved the involution process during the first 24 days (p < 0.05). The prevalence of pathogenic bacteria found in in vitro cultures was significantly variable (p < 0.01), as were the antibiotic sensitivity patterns. Pathogenic bacteria isolates decreased after MPFF applications in a dose–response fashion (p < 0.01), while isolates obtained from controls and low-dose-MPFF-treated animals were stable and similar (p > 0.05). The sensitivity patterns of pathogenic bacteria isolated in in vitro cultures from MPFF-treated animals were variable, although resistance to E. coli, Staphylococcus aureus, Bacillus spp., and coliforms was shown irrespective of the MPFF doses used. However, MPFF-treated cows showed a dose–response effect regarding PMN rates (p < 0.05). The calving-first service, calving–conception interval, and conception rate improved significantly from using higher MPFF doses (p < 0.05). In conclusion, this study shows that MPFF treatment differentially affects uterine involution, bacteriological profiles, cytological traits, and reproductive performance in metritis-positive dairy cows naturally infected by E. coli.

Lymphotonic activity of Ruscus extract, hesperidin methyl chalcone and vitamin C in human lymphatic smooth muscle cells

Besides actions including their venotonic, anti-inflammatory, and anti-oxidant effects, venoactive drugs are expected to act on edema via their action on lymphatics. The objective of this study was to evaluate the effect of the combination of Ruscus, hesperidin methyl chalcone and Vitamin C (Ruscus/HMC/Vit C) on intracellular calcium mobilization and contraction of human lymphatic smooth muscle cells (LSMCs) to better characterize the mechanism of its lymphotonic activity. Calcium mobilization was evidenced by videomicroscopy analysis of the fluorescence emitted by a specific Ca2+ sensitive dye and measured after injection of Ruscus/HMC/Vit C at 0.1, 0.3, 1.0, and 3.0mg/mL into LSMCs. Ruscus/HMC/Vit C induced a strong and reproducible concentration-dependent calcium mobilization in LSMCs. On the contrary, another venoactive drug used as comparator, micronized purified flavonoid fraction (MPFF), did not induce calcium mobilization whatever the tested concentration. Although alternative mechanisms of action may result in potential lymphotonic effects, the efficacy of lymphotonic products is nonetheless related to their stimulating effect on the contractile activity of the smooth muscle cells surrounding lymphatic vessels. In the light of the results obtained in this study, the direct effect of Ruscus/HMC/Vit C on LSMC contraction may partially explain its clinical efficacy on lymphotonic activity, as has been observed in terms of objective signs of edema as reported in the recent guidelines on chronic venous disease.

Conservative treatment of pelvic venous disease

Pelvic venous incompetence (PVI), although usually asymptomatic, may cause pelvic venous disease (PeVD), which may clinically manifest through pelvic symptoms, particularly chronic pelvic pain (CPP). There is no standard approach to manage PeVD and, therefore, the treatment should be individualized based on symptoms and the patient"s needs. To date, many treatment methods have been proposed, including conservative treatment, pelvic vein embolization, and reparative surgery. Medical treatment of CPP due to PVI includes non-steroidal anti-inflammatory drugs (NSAIDs), medical suppression of ovarian function, venoprotective agents, vasoconstrictor drugs, and psychotropic agents. The NSAIDs have a short-term efficacy and, due to side effects after longer use, they should be avoided as a long-term solution. Pharmacological suppression of ovarian function may result in CPP relief and may be achieved using medroxyprogesterone acetate, gonadotropin-releasing hormone (GnRH) agonist, long-acting reversible contraceptives, and danazol. They have been proven to be effective in the treatment of pelvic symptoms of PeVD. Venoactive drugs (VADs), particularly micronized purified flavonoid fraction (MPFF) and psychotropic agents, also provide an improvement in CPP related to PVI. A conservative approach represents the first-line treatment modality. It is reasonable to offer such treatment initially, reserving more invasive approaches for resistant cases and patients who present with side effects to the conservative management.

Clinical Efficacy of Conservative Treatment with Micronized Purified Flavonoid Fraction in Female Patients with Pelvic Congestion Syndrome.

IntroductionPelvic congestion syndrome (PCS) may be effectively managed with conservative treatment in certain patients. Treatment with venoactive drugs is common, but supportive data are limited. This study evaluated the clinical efficacy of micronized purified flavonoid fraction (MPFF) in women with PCS.MethodsIn a single-blind, placebo-controlled study, women with duplex ultrasound diagnosis of pelvic varicose veins (PVV) and PCS were randomized to MPFF 1000 mg once daily or placebo for 2 months. Clinical manifestations of PCS were evaluated at baseline and end of treatment (M2) using three assessment tools: disease-specific quality of life (QoL) Pelvic Varicose Vein Questionnaire (PVVQ), Pelvic Venous Clinical Severity Score (PVCSS), and the Visual Analog Scale (VAS) for the main symptoms of the disease.ResultsA total of 83 women were included, 42 received MPFF and 41 received placebo.In the MPFF group, the mean global PVVQ QoL index decreased significantly from 45.1 ± 14.7 at baseline to 36.6 ± 10.6 at M2 (mean change: 8.2 ± 10.4); no significant change was observed in the control group (mean change: – 0.3 ± 4.0). The between-group difference was statistically significant (P < 0.001). Compared with control, significant improvements were observed in all four QoL parameters (pain, physical, social, psychological, all P < 0.001).The mean PVCSS summary score decreased significantly by 3.4 ± 3.4 in the MPFF group (P < 0.001) compared with a non-significant change of – 0.2 ± 1.6 in the control group (between-group difference P < 0.001). In the MPFF group, improvements were statistically significant for 6 out of 10 clinical manifestations of PCS measured using the PVCSS, including pain (mean change from baseline: 0.5 ± 0.7) heaviness (0.4 ± 0.7), discomfort (0.6 ± 0.7) and tenderness (0.3 ± 0.5). No significant improvements were observed in the control group. When measured by VAS, between-group differences were statistically significant for the overall summary score (P < 0.001) and for 8 out of 10 PCS symptoms, including: pain (mean MPFF change from baseline: 2.0 ± 2.2), heaviness (1.3 ± 2.1), discomfort (1.5 ± 2.0), tenderness (0.9 ± 1.9), and edema (1.3 ± 2.1).ConclusionIn women with PCS, conservative treatment with MPFF was associated with improved QoL and reduced symptom severity. MPFF may be considered an effective and safe treatment option for PCS in routine clinical practice.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40122-021-00312-6.

Is There a Difference in the Clinical Efficacy of Diosmin and Micronized Purified Flavonoid Fraction for the Treatment of Chronic Venous Disorders? Review of Available Evidence.

Flavonoids are oral venoactive drugs frequently prescribed to relieve the symptoms of chronic venous disorders (CVD). Among venoactive drugs, diosmin is a naturally occurring flavonoid glycoside that can be isolated from various plant sources; it can also be obtained after conversion of hesperidin extracted from citrus rinds. Micronized purified flavonoid fraction (MPFF) is a preparation that contains mainly diosmin and a small fraction of hesperidin. We performed a state-of-the-art literature review to collect and analyze well-conducted randomized clinical studies comparing diosmin – also called non-micronized or hemisynthetic diosmin – 600 mg a day and MPFF, 1000 mg a day. Three clinical studies met the criteria and were included for this literature review. These clinical studies showed a significant decrease of CVD symptom intensity (up to approximately 50%) and global patient satisfaction after one-to-six-month treatment with diosmin or MPFF, without statistical differences between these two forms of diosmin. Both treatments were well tolerated with few mild adverse drug reactions reported. Overall, based on this literature review, there is no clinical benefit to increase the dose of diosmin beyond 600 mg per day, to use the micronized form, or to add hesperidin, since clinical efficacy on venous symptomatology is achieved with 600 mg per day of pure non-micronized diosmin. This challenges the status of diosmin – 600 mg a day – in guidelines for the management of CVD, which is currently categorized 2C (weak recommendations for use and poor quality of evidence), while the most widely used and assessed preparation MPFF is rated 1B (strong recommendation for use and moderate quality of evidence).

Clinical effectiveness of bioflavonoids in the treatment of secondary lower limb lymphedema

AIM: This study aimed to investigate the effectiveness of the application of a combination of the preparation of micronized purified flavonoid fraction (MPFF) and elastic compression in patients with acquired lymphostasis.&#x0D; MATERIALS AND METHODS: Sixty patients with stage II secondary lower limb lymphedema according to М. Foeldi were included. The patients were divided into two groups through randomization with the envelope method. The first group (n = 30) was subjected to a conservative treatment (MPFF, 1000 mg/day) coupled with elastic compression (3rd class compression stockings). The second group was given compressive therapy (third-class compression stockings). The patients were physically examined through the measurement of the circumference of the limb at different levels.&#x0D; RESULTS: In the first group, the circumference of the lower third of the shin decreased by 8.15% (p = 0.005) after 1 month and by the end of treatment by 10.6% (p 0.001), of the middle third of shin by 3.15% (p = 0.001) and 4.78% (p 0.001), and of the upper thirdby 4.08% (p 0.001) and 5.99% (p 0.001). By the end of the observation period (3 months), the circumference of the lower third of the shin in the second group (29.68 4.67 cm) was significantly greater than that in the first group (26.65 2.92 cm, p = 0.035). No adverse reactions were observed in the MPFF group.&#x0D; CONCLUSIONS: The volume of the lower limbs of patients with acquired lymphedema decreased after using a combination of MPFF and elastic compression to a larger extent than after the isolated use of elastic compression. Patients taking MPFF had a positive clinical effect without adverse reactions. Therefore, MPFF could be used in the pharmacotherapy of secondary lymphedema of the lower limbs.

Time course of microvalve pathophysiology in high pressure low flow model of venous insufficiency and the role of micronized purified flavonoid fraction.

The aim of this study was to characterize, in an experimental model, the mechanisms involved in the initiation of venous insufficiency at the level of microvenous valve and whether they can be influenced by early treatment with micronized purified flavonoid fraction (MPFF). The external right iliac vein of 78 male golden Syrian hamsters was ligated to induce chronic venous insufficiency. Internal venular diameter as well as leukocyte-endothelium-interaction (leukocytes sticking after staining with rhodamine 6G), were assessed using an intravital microscope. In the second part of the study 30 animals were divided into three groups and underwent: ligation plus MPFF, ligation plus 10% lactose solution (vehicle), or sham operation. Treatment with MPFF 100 mg/kg/day or vehicle started 2 days before ligation and lasted for 7 days. Venular diameter and number of adherent leukocytes were assessed 5 days post-ligature. Venular diameter increased immediately after ligature and reached a maximum at 4 hours (P<0.001 vs. baseline), followed by a plateau before gradually returning to baseline dimensions. The increase in the number of adherent leukocytes was also immediate but attained maximal number at 3 days (P<0.0001), followed by a plateau and then gradual return to baseline numbers. In MPFF-treated animals, leukocyte adhesion to the microvalves was prevented compared with vehicle-treated animals (P<0.0001) and venular diameter was also significantly reduced (P<0.05). Venous hypertension induced immediate venular dilatation followed by an increase in the number of adherent leukocytes at microvalve level. Treatment with MPFF prevented the initiation of microvalve inflammation and may play a protective role in the progression of chronic venous insufficiency.

PHLEBOPROTECTORS BASED ON FLAVONOIDS: DOSAGE FORMS, BIOPHARMACEUTICAL CHARACTERISTICS, TECHNOLOGICAL FEATURES

Micronized purified flavonoid fraction (MPFF) is the original phlebotropic drug. Its marketed form (Detralex®) consists of 90% diosmin and 10% of other flavonoids. Calculated as hesperidin, it is the most widely used drug today. Diosmin and hesperidin, which are parts of the majority of venoactive drugs, are sparingly water-soluble compounds, and this feature can effect on their clinical efficacy. One of the ways to increase the solubility of these compounds leading to an increase in bioavailability, is the micronization of the active ingredients.The aim of the investigation is a comparative determination of the dynamics and dissolution efficiency of the drugs containing bioflavonoid fractions in the dissolution test, as well as the analysis of the micronization degree and its impact on technology and biopharmaceutical parameters.Materials and methods. A biopharmaceutical release profile was determined using HPLC. Disintegration, characteristics of the shape and size of the tablets’ particles were determined according to the methods of the State Pharmacopoeia of the XIV-th edition.Results. The objects created with the use of diosmin and hesperidin, have been considered in detail. The role of technological solutions in relation to the corresponding dosage forms is notified. Detailed biopharmaceutical characteristics have been established with a choice of HPLC-based release control methodology. All the drugs in this group have a low water solubility leading to the maximum bioavailability for Detralex® which is about 1.26%; and no more than 0.2% for other analyzed models.Conclusion. Detralex® dominates among the analyzed objects (tablets) in terms of the release rate. With regard to the overall quantitative indicators of release, the actual numbers are quite low, which is associated with the poor water solubility of the active substances.

Micronized purified flavonoid fraction in the treatment of hemorrhoidal disease.

Hemorrhoidal disease (HD) is common in adults. Treatment is largely conservative, although more invasive procedures may be required. Venoactive drugs such as micronized purified flavonoid fraction (MPFF) are widely used, but a recent and comprehensive review of supporting evidence is lacking. In acute HD, MPFF can reduce HD symptoms such as bleeding, pain, anal discomfort, anal discharge and pruritus. In patients undergoing surgery, postoperative adjunct MPFF consistently reduces pain, bleeding durationand use of analgesia. MPFF treatment is appropriate and effective both as a first-line conservative treatment and as a postoperative adjunct treatment. MPFF reduces the duration of hospital stay following surgery, facilitating a return to normal activity and improving quality of life. MPFF may also prevent HD recurrence.

Efficacy of two micronized purified flavonoid fraction dosing regimens in the pelvic venous pain relief.

The venoactive drug treatment regimen for pelvic venous disorders (PeVDs) is not finally established. The study aimed at assessing the efficacy of micronized purified flavonoid fraction (MPFF) in a standard or double dose in the pelvic venous pain (PVP) relief in PeVD. We analyzed the treatment efficacy in 125 female patients with PeVD, who were allocated to two groups with MPFF treatment in a regular dose of 1000 mg once daily (OD) for 2 months (N.=65; group 1) or double dose of 1000 mg twice daily for 1 month and then 1000 mg OD for 1 month (N.=60; group 2). Patients underwent clinical examination along with an assessment of the PVP severity using the visual analogue scale (VAS) ranged from 0 to 10 scores, transvaginal and transabdominal duplex ultrasound scanning (DUS), and single-photon emission computed tomography (SPECT) of the pelvic veins with in vivo-labelled red blood cells (RBCs). The groups were different at baseline in the PVP severity (3.4±1.2 vs. 7.3±0.5 scores in groups 1 and 2, accordingly; P=0.012). DUS and SPECT were used to evaluate diameters of gonadal, parametrial, and uterine veins, to assess the presence of reflux in them, to measure blood flow velocity in the internal iliac veins (V<inf>lin IIV</inf>), and to calculate the coefficient of pelvic venous congestion (C<inf>PVC</inf>). The treatment was associated with a significant reduction in the PVP score from 3.4±1.2 to 1.2±0.2 (P=0.03) when using the standard dose for 2 months and from 7.3±0.5 to 0.8±0.1 (P=0.001) when using the double dose in the 1st month. The PVP relief was achieved on average after 13.7±0.6 and 3.1±0.8 days in groups 1 and 2, accordingly (P=0.0001 between the groups). At month 2, the C<inf>PVC</inf> reduction was found to be significantly greater in group 2 compared to group 1 (46.6% vs. 25%; P=0.018). Side effects (gastralgia, flatulence) were reported by only 2 (3.3%) patients of group 2. The venoactive drug therapy with MPFF is an effective and safe option for the PVP relief in female patients with PeVD. The use of double dose in the 1st month seems to be appropriate in patients with greater PVP severity but is associated with an increased rate of side effects.

Pending questions in venous ulcers management. Report from a Symposium of the World Union of Wound Healing Societies International Congress

Venous ulcers represent the most frequent ulcers and have a high clinical and socioeconomic significance. Nevertheless, pending questions remain on epidemiology, genetic and biomolecular mechanisms, contraindications and risk factors of compression therapy, role of pharmacological therapy. Overall prevalence in the range of 1-2% and point prevalence of 0.08-0.6% can be reduced if risk factors are identified and treated early. In this context, analysis of factor XIII and hemocromatosis gene polymorphisms, with the C282Y and H63D variants, may be of great importance. Also MMP12 gene polymorphism and the imbalance between matrix metalloproteinases and their tissue inhibitors are able to impair wound healing via deleterious degradation process of extra-cellular matrix. From a therapeutic point of view, conflicting recommendations exist on relative contraindications, risks and adverse events of compression therapy. Some studies showed that the administration of pentoxyphilline, Micronized purified flavonoid fraction (MPFF) and sulodexide was effective in accelerating ulcer healing, but there is no data on the duration of treatment, recurrence rates and cost-effectiveness relationship.